title: Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma.
abstract: OBJECTIVE
  Our aim was to examine the prognostic significance of ERbeta1 and ERbeta2 expression in ERalpha-negative breast carcinomas.
  
  
  METHODS
  We evaluated nuclear and cytoplasmic expression of ERbeta1 and ERbeta2 by immunohistochemistry in a group of 95 patients with long follow-up. ERbeta1 and ERbeta2 status was correlated with clinicopathological parameters and disease outcome. Univariate and multivariate analyses of ERbeta1 and ERbeta2 as independent markers of disease-free survival (DFS) were carried out using the Cox proportional hazards model.
  
  
  RESULTS
  Nuclear ERbeta1 (nERbeta1) and nERbeta2 status was positively correlated (p = 0.01). nERbeta1 positivity was associated with low histological grade (p = 0.01) in all patients and in the nERbeta2-positive subgroup (p = 0.03) but not in the nERbeta2-negative (p = 0.27). nERbeta2 positivity was associated with lymph node involvement and tumor relapse in all cases (p < 0.00 and p < 0.00, respectively) and in the nERbeta1-negative subgroup (p < 0.00 and p < 0.00, respectively) but not in the nERbeta1-positive (p = 0.09 and p = 0.20, respectively). nERbeta2 positivity was associated with poor DFS in all patients (log-rank p <0.00), in the post-menopausal patient subgroup (log-rank p = 0.02) and in the HER2-negative (triple-negative) subgroup (log-rank p = 0.04). Cox multivariate analysis including ERbeta1, ERbeta2 and established clinicopathological variables highlighted ERbeta2 as an independent marker of early disease recurrence (hazard ratio 4.87; 95 % confidence interval 1.07-22.3; p = 0.04).
  
  
  CONCLUSIONS
  High nERbeta2 is an independent marker of early relapse in ERalpha-negative breast carcinoma, and in particular, in the nERbeta1-negative, the post-menopausal patient and the triple-negative subgroups. These findings suggest that inhibition of expression and/or function of ERbeta2 could improve disease outcome.
authors.affiliation: Laboratory of Histology and Embryology, Medical School, University of Athens, 75 M. Asias str., 11527, Athens, Greece.
authors.forename: Nuiki Iota
authors.initials: NI
authors.lastname: Chantzi
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
authors.forename: Marina
authors.initials: M
authors.lastname: Palaiologou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Goutas
authors.forename: Theodoros
authors.initials: T
authors.lastname: Filippidis
authors.forename: Stamatis D
authors.initials: SD
authors.lastname: Vassilaros
authors.forename: Eugen
authors.initials: E
authors.lastname: Dhimolea
authors.forename: Dimitra J
authors.initials: DJ
authors.lastname: Mitsiou
authors.forename: Muichael N
authors.initials: MN
authors.lastname: Alexis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta